We have developed two model systems utilizing the concept of sex steroid imprinting to program the development of prostatic cancer. One of the models involves the castration of Wistar rats at birth and daily treatment with estrogen from day 1 to day 30. The treatment was found to induce squamous cell carcinoma of the prostate whereas non-castrates treated similarly failed to develop such lesions (Arai et al., Gann, 69: 861, 1978). The second model involves the programming of prostatic cancer formation in Noble rats. The tumor incidence and latency period of tumor formation will be assessed. At present, we have developed several sensitive assay systems that may provide us with useful markers for identifying phenotypically the stages of differentiation of prostatic cancer cells. We have developed a two-dimensional gel electrophoretic system that allowed us to detemmine lobular differences in tissue protein profiles. The net amino acid incorporation into tissue proteins, as judged by radioautography, suggests significantly higher activity in cells that destined to undergo neoplastic transformation. A high pressure liquid chromatographic system is currently being developed for separation of testosterone and it's metabolites. The possible microsomal involvement in the formation of 7 alpha, 6 beta and 16 alpha-OH testosterone metabolite is under investigation. Such enzymatic pathways are also found in the liver. The 16 alpha-hydroxylase activity appears to be programmed by neonatal androgen. We have isolated a form of cytochrome P-450 from hepatic microsomes of male rats that will catalyze 16 alpha-hydroxylation of testosterone in a reconstituted system. Immunochemical identify of hepatic and prostatic cytochrome P-450 awaits further investigation.